title: A structural model of the human thrombopoietin receptor complex.
abstract: Thrombopoietin (TPO) is a glycoprotein hormone that regulates red blood cell production. Presented here is a modeling study of the extracellular region of the human thrombopoietin receptor complex, in particular the TPO-receptor interface. The models were developed from structural homology to other cytokines and their receptors. Experimental evidence suggests that the receptor is homodimeric and it was modeled accordingly. Key interactions are shown that correlate with previous cytokine receptor complexes, and the pattern of cysteine bonding (Cys7-Cys151 and Cys29-Cys85) agrees with that experimentally determined for thrombopoietin. These models pave the way for possible mutagenesis experimentation and the design of (ant)agonists.
authors.affiliation: Physical and Theoretical Chemistry Laboratory, University of Oxford, United Kingdom.
authors.forename: C M
authors.initials: CM
authors.lastname: Deane
authors.forename: R T
authors.initials: RT
authors.lastname: Kroemer
authors.forename: W G
authors.initials: WG
authors.lastname: Richards
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003196:Computer Graphics; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009363:Neoplasm Proteins; D011487:Protein Conformation; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000378:metabolism; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D016415:Sequence Alignment; D013926:Thrombopoietin / Q000737:chemistry* / Q000378:metabolism
chemical_list: D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; D013926:Thrombopoietin